Abstract
Molecular and cellular adaptations in nucleus accumbens (NAc) medium spiny neurons (MSNs) underlie stress-induced depression-like behavior, but the molecular substrates mediating cellular plasticity and activity in MSN subtypes in stress susceptibility are poorly understood. We find the transcription factor early growth response 3 (EGR3) is increased in D1 receptor containing MSNs of mice susceptible to social defeat stress. Genetic reduction of Egr3 levels in D1-MSNs prevented depression-like outcomes in stress susceptible mice by preventing D1-MSN dendritic atrophy, reduced frequency of excitatory input and altered in vivo activity. Overall, we identify NAc neuronal-subtype molecular control of dendritic morphology and related functional adaptations, which underlie susceptibility to stress.
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Acknowledgements
We thank Brian N. Mathur and Scott M. Thompson (UMSOM) for input on electrophysiology experiments. This work was supported by NIMH R01MH106500, NIDA R01DA038613 and The One Mind / Janssen Rising Star Translational Research Award.
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Francis, T., Chandra, R., Gaynor, A. et al. Molecular basis of dendritic atrophy and activity in stress susceptibility. Mol Psychiatry 22, 1512–1519 (2017). https://doi.org/10.1038/mp.2017.178
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DOI: https://doi.org/10.1038/mp.2017.178
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